This proposal is aimed at applying two different approaches to immunotherapy of tumors in inbred mice. The approaches we plan to study are based on model systems developed during the course of investigations into basic mechanisms underlying regulatory cellular interactions in the mammalian immune system. One approach makes use of the well established phenomenon of the allogeneic effect by which allogeneic T lymphocytes provide a stimulus that can profoundly facilitate effective host immune reactivity against a variety of antigens. Existing preliminary evidence demonstrated the feasibility of this approach in enhancing host resistance to syngeneic tumors. The second approach is based on a detailed analysis of suppressor mechanisms in the immune response to tumors, and their effects on the expression of host tumor-specific immunity. Recent studies suggested that suppressor cells regulate the magnitude of the immune response to various antigens, and that these responses can be augmented by the depletion of suppressor cells. Thus we intend to study in detail the role of suppressor cells, or factors made by them, in tumor immunity and to establish procedures for depleting such cells, and thus, to increase the net anti-tumor effector response. These studies will be conducted by using in parallel in vitro and in vivo assays of tumor immunity. It is expected that these approaches will result in an augmented immune response to tumors and will enable us to establish more effective methods for the immunotherapy of cancer.